Overlap and effective size of the human CD8+ T cell receptor repertoire.

Publication Type:

Journal Article

Source:

Science translational medicine, Volume 2, Issue 47, p.47ra64 (2010)

Keywords:

2010, Adult, CD8-Positive T-Lymphocytes, Clinical Research Division, Complementarity Determining Regions, Female, Flow Cytometry Core Facility, Genomics Core Facility, HLA Antigens, Humans, Immunologic Memory, Male, Middle Aged, Public Health Sciences Division, Receptors, Antigen, T-Cell, Shared Resources, Young Adult

Abstract:

Diversity in T lymphocyte antigen receptors is generated by somatic rearrangement of T cell receptor (TCR) genes and is concentrated within the third complementarity-determining region 3 (CDR3) of each chain of the TCR heterodimer. We sequenced the CDR3 regions from millions of rearranged TCR beta chain genes in naïve and memory CD8(+) T cells of seven adults. The CDR3 sequence repertoire realized in each individual is strongly biased toward specific V(beta)-J(beta) pair utilization, dominated by sequences containing few inserted nucleotides, and drawn from a defined subset comprising less than 0.1% of the estimated 5 x 10(11) possible sequences. Surprisingly, the overlap in the naïve CD8(+) CDR3 sequence repertoires of any two of the individuals is approximately 7000-fold larger than predicted and appears to be independent of the degree of human leukocyte antigen matching.